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Previous studies have shown that overexpression of the protein PSD-95 (postsynaptic density-95) selectively enhances AMPA receptor-mediated synaptic responses in hippocampal pyramidal cells. To determine whether this effect is related to synaptic plasticity at these synapses, we examined whether PSD-95 expression mimics long-term potentiation (LTP), and(More)
Epilepsy affects more than 0.5% of the world's population and has a large genetic component. It is due to an electrical hyperexcitability in the central nervous system. Potassium channels are important regulators of electrical signalling, and benign familial neonatal convulsions (BFNC), an autosomal dominant epilepsy of infancy, is caused by mutations in(More)
Trafficking of AMPA receptors (AMPA-Rs) to and from synapses controls the strength of excitatory synaptic transmission. However, proteins that cluster AMPA-Rs at synapses remain poorly understood. Here we show that PSD-95-like membrane-associated guanylate kinases (PSD-MAGUKs) mediate this synaptic targeting, and we uncover a remarkable functional(More)
Synaptic plasticity involves protein phosphorylation cascades that alter the density of AMPA-type glutamate receptors at excitatory synapses; however, the crucial phosphorylated substrates remain uncertain. Here, we show that the AMPA receptor-associated protein stargazin is quantitatively phosphorylated and that stargazin phosphorylation promotes synaptic(More)
The functions of some CLC Cl(-) channels are evident from human diseases that result from their mutations, but the role of the broadly expressed ClC-2 Cl(-) channel is less clear. Several important functions have been attributed to ClC-2, but contrary to these expectations ClC-2-deficient mice lacked overt abnormalities except for a severe degeneration of(More)
Renal salt loss in Bartter's syndrome is caused by impaired transepithelial transport in the loop of Henle. Sodium chloride is taken up apically by the combined activity of NKCC2 (Na+-K--2Cl- cotransporters) and ROMK potassium channels. Chloride ions exit from the cell through basolateral ClC-Kb chloride channels. Mutations in the three corresponding genes(More)
1. ClC proteins are a class of voltage-dependent Cl- channels with several members mutated in human diseases. The prototype ClC-0 Torpedo channel is a dimeric protein; each subunit forms a pore that can gate independently from the other one. A common slower gating mechanism acts on both pores simultaneously; slow gating activates ClC-0 at hyperpolarized(More)
Synaptogenesis is required for wiring neuronal circuits in the developing brain and continues to remodel adult networks. However, the molecules organizing synapse development and maintenance in vivo remain incompletely understood. We now demonstrate that the immunoglobulin adhesion molecule SynCAM 1 dynamically alters synapse number and plasticity.(More)
Synapses are asymmetric cell junctions with precisely juxtaposed presynaptic and postsynaptic sides. Transsynaptic adhesion complexes are thought to organize developing synapses. The molecular composition of these complexes, however, remains incompletely understood, precluding us from understanding how adhesion across the synaptic cleft guides synapse(More)
AMPA receptors mediate the majority of fast synaptic transmission and underlie several forms of synaptic plasticity. AMPARs also have an important role in several neuronal pathologies. Therefore, studying the structure and function of these receptors is important for understanding general mechanisms of synaptic transmission as well as for the development of(More)